The proposed study will comparatively evaluate three hypotheses regarding biopsychological mechanisms underpinning atypical empathy in conduct disorder (CD). Significance: Antisocial behavior across the lifespan creates an enormous public health burden. Despite the indisputable importance of social factors, much remains to be learned about neurobiological factors involved in childhood CD. Empathic concern for others has been hypothesized to play a key role in inhibiting aggression and other forms of antisocial behavior and deficits in empathy lead to profound disturbances in social interaction. Therefore, studies of the role of atypical empathic concern in childhood CD are of great importance. Innovation: The proposed study would be the first neurobiological study of atypical empathy in pre-adolescent children with CD using functional magnetic resonance imaging. It will provide the empirical basis for a much-needed integrative biopsychological model of the basic brain-behavior processes involved in dysfunctional empathy in CD. Multiple levels of scientific analysis are fundamentally important when addressing complex phenomena such as CD. Too often, the assessment of empathy in both healthy and psychiatric populations has relied solely on self-report measures that provide only one kind of information. Approach: To achieve our scientific aims we will obtain from male and female 9-11 year old children who meet diagnostic criteria for CD (N = 60) and a group of non-CD control children (N = 60) a number of neurobiological and behavioral measures of responses to viewing others in pain. These measures include: (a) structural brain anatomy and functional connectivity (b) neuro-hemodynamic responses to visual stimuli that typically evoke empathic concern, (c) subjective ratings of the affect elicited by viewing others in pain, (d) behavioral measures of approach tendencies to stimuli depicting pain in others, and (e) measures of autonomic nervous system activity. We hypothesize that when viewing others in pain, children with CD will exhibit greater neuro-hemodynamic response in areas of the pain matrix involved in both the sensory-discriminative and affective aspects of the first-hand experience of pain. The behavioral measures will indicate that children with CD experience a more positive affective response to seeing others in pain than comparison children. Furthermore, children with CD will exhibit both less anatomical connection and functional connectivity between the PFC and the amygdala, which would be consistent with diminished self-regulation of emotional aspects of empathic concern for others in distress. Environment and Investigators: Our experienced team of investigators and consultants includes experts on CD, functional neuroimaging and cognitive neuroscience, especially in the area of empathy, and psychophysiological measurement. The University of Chicago provides a strong environment and resources for this project. PUBLIC HEALTH RELEVANCE: Because most crime is committed by juveniles, antisocial behavior in youth creates an enormous public health burden. Antisocial behavior not only harms victims in physical and psychological ways, but antisocial youth are at high risk for incarceration, injury and death from violence, substance abuse, and suicide. The proposed translational study will lead to an integrative understanding of basic brain-behavior processes involved in dysfunctional empathic concern in children with conduct disorder and suggest new approaches to treatment and prevention.